RSV is a virus that causes respiratory tract infections, and cells infected with the virus form multinucleated giant cells (syncytia). RSV can cause infection at any age during our lifetime, but it is the pathogen that causes very severe symptoms in especially infants. Fifty to seventy percent or more of infants get infected with this virus within a year after birth, and almost all the children acquire antibody by the age of 3. However, infection within several weeks to several months after birth causes most severe symptoms. In the case of low-birth-weight babies or children with impaired immunity or underlying cardiorespiratory disease, the risk of increased severity increases. There is a report that the fatality rate from RSV infection is 1 to 3%. However, the fatality rate widely varies depending on the situation. It has been reported during the 1980s that the fatality rate is as high as 37% according to research on hospitalized children with underlying heart disease.
RSV infections have been reported all over the world irrespective of geographic or climatic conditions. Characteristically, RSV infections cause severe symptoms in immature infants in all the areas, and repeatedly break out every year in especially urban areas.
It has been reported that RSV infections account for about 50% of cases of pneumonia and 50 to 90% of cases of bronchiolitis in infants. The peak of the number of children hospitalized with lower respiratory tract disease, such as pneumonia or bronchiolitis, coincides with the peak of outbreak of RSV infections rather than influenza. During epidemics of RSV infections, RSV reinfection in older children or adults universally occurs. However, in contrast to severe symptoms in infants, older children or adults show only mild cold-like symptoms and often get better.
It is known that RSV is relatively unstable in the environment, but transmission of RSV infection efficiently occurs within families. A school-age child showing mild symptoms often introduces the virus into the family. There is also a report that 44% of families with a school-age child and an infant have an experience of intrafamilial transmission of RSV infection during its epidemic season. Main routes of RSV infection are large respiratory droplets and contact through hands or objects contaminated with respiratory secretions. Particularly, RSV infection occurs via close contact. Therefore, in order to prevent RSV infection in an infant, it is very important to accurately understand the presence or absence of RSV infection in other family members irrespective of the severity of symptoms. When any of the family members is confirmed RSV infection, it is very important to avoid contact with the infant and prevent contamination from secretions.
From the viewpoint of prevention and treatment of RSV infections, especially RSV infection in infants, there has been demand for a simple and higher-sensitive kit for rapidly diagnosing RSV infection. It is preferred that RSV-infected infants are appropriately treated as soon as possible, which requires a high-sensitive test kit that can give a test result in a short time but does not give a false-negative result even when a test is performed in an initial phase of infection in which the amount of the virus is small. Further, when a member of a family with an infant shows cold-like symptoms and is suspected of RSV infection, a simple test method is required by which the presence or absence of RSV infection can be determined with less physical and financial burden.
As simple, high-sensitive, and rapid diagnostic kits that satisfy such a requirement, immunochromatographic RSV test kits have been developed. Currently, more than one immunochromatographic test kit is known which can detect a virus antigen and can be used to assist the diagnosis of RSV infections. However, all these kits use antibodies against F protein of RSV (Patent Literatures 1 to 3).
The F protein of RSV is one of the two kinds of main glycoproteins present on the surface of RSV. On the surface of the virus, G protein is also present in addition to the F protein. The F protein is highly conserved between and within the subtypes A and B of RSV in homology, whereas the homology of the G protein between the subtypes is only about 53%. Research conducted by Beeler and Coelingh (1989) demonstrates that antibodies against the F protein of RSV can bind to all 14 clinical isolates isolated in various regions in the United States of America and Australia from 1956 to 1985 and the F protein is very highly conserved among the virus strains (Patent Literature 4, Non-Patent Literature 1).
Antibodies against the F protein have been used in RSV detection kits with the expectation that various clinical isolates can be detected without exception due to highly-conserved epitopes. However, RSV detection using such conventional RSV test kits involves a major problem that 30 to 40% of samples determined as positive by another test method are determined as negative. The reason why immunochromatographic test kits are likely to give false-negative results have been considered that antibodies against the F protein used in those kits do not have sufficient binding affinities. If the binding affinities are not sufficient, clear positive signals cannot be detected when the amount of the virus contained in samples are small and consequently, the samples are judged as false negative. In order to develop a high-sensitive test kit in which a clear signal can be detected even when the amount of the virus is small, an attempt has been made to prepare a monoclonal antibody having a high affinity for the F protein of RSV (Patent Literature 5). However, it is very difficult to develop an RSV test kit which can detect clinical isolates without exception as well as can achieve a practical positive detection rate, simply by increasing the affinity of an antibody for the F protein.